The long-range goals of the experiments described in this application are to understand the anatomical and molecular underpinnings which determine the accuracy of peripheral nerve regeneration. The present proposal addresses accuracy of peripheral nerve regeneration at the nerve trunk level, within the context of "preferential motor reinnervation". Preferential motor reinnervation (PMR) refers to the fact that during regeneration of rat femoral nerve, a mixed peripheral nerve, motor axons have been shown to preferentially, albeit incompletely, reinnervate a terminal motor vs sensory distal nerve branch. Our preliminary studies have lead to two major discoveries that shape our proposed experiments: 1) the addition of growth factors to the nerve repair site significantly enhances PR; and 2) BDNF mRNA levels are differentially regulated in the terminal motor and sensory nerve trunks following femoral nerve transection. This proposal has three main parts. The first will be to determine, on an in vivo level, the mechanism by which the addition of specific growth factors to a nerve transection site increase preferential motor reinnervation. The second part will determine if PMR is dependent upon the presence of living Schwann cells. Finally, we will analyze the potential involvement of the neurotrophins and ciliary neuronotrophic factor, and we will use uniquely powerful molecular techniques to demonstrate differentially expressed gene products that may underlie the accuracy of regeneration in this model system. Gaining insight into the cellular and molecular underpinnings which determine the accuracy of nerve regeneration in these animal models has direct relevance to human peripheral nerve repair.